The signaling capacity of these molecules in NK cells suggest potential avenues for the use of recombinant constructs of ICOS and ICOS-L, or specific Abs for the therapeutic manipulation of NK immune responses and provides the basis for future studies in which the targeting of the ICOS/ICOS-L axis may support new strategies to characterize and manage these immunodeficiencies. This evidence concerns the gene ICOS and immunodeficiency disease.